OBJECTIVES: To assess the cost-effectiveness of dasatinib 100 mg/day vs. imatinib 600 mg/day, imatinib 800 mg/day and versus nilotinib 800 mg/day in patients with chronic myeloid leukaemia (CML) in the chronic phase of the disease, resistant to prior therapy with imatinib 400 mg/day from the perspective of the Portuguese National Health Service (NHS). METHODS: A cost-utility Markov model was developed by BMS for NICE appraisal and has been adapted to the Portuguese treatment practice. Four health states were considered, three represented CML phases (chronic, accelerate and blast) and the death state with one-month cycles. The model was populated with efficacy data from clinical trials, resource utilization by expert opinion, published quality of life data  for CML laypersons in the UK and unit prices from official 2010 price lists. A life-long, NHS perspective was used and deterministic results were determined.  A deterministic sensitivity analysis was performed to test the robustness of the results.  RESULTS: The results showed that chronic phase CML patients resistant to standard dose imatinib gain on average 2.72 life-years, or 2.38 quality adjusted life-years, when treated with dasatinib 100 mg/day compared with imatinib 600 mg/day or compared to imatinib 800 mg/day and on average 0.53 life-years, or 0.47 quality adjusted life-years compared to nilotinib 800 mg/day. The incremental cost per quality adjusted life year gained (QALY) amounts to €39,941 when dasatinib 100 mg/day is compared with imatinib 600 mg/day, and to €14,470 when compared to imatinib 800 mg/day and to €29,422 when compared to nilotinib during a lifetime period. CONCLUSIONS: The results indicate that dasatinib is a cost-effective option in CML patients resistant to standard-dose imatinib in Portugal in comparison with high-dose imatinib and nilotinib.